POlyfunctional PNAs for Precision RNA Targeting and modulation of interactions with proteins – POPNART

Funder: Project funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.4 – Cascade Call related to the Program “National Center for Gene Therapy and Drugs based on RNA Technology (CN RNA & GENE THERAPY) – Spoke 6” funded by the European Union – NextGenerationEU;

Award Number: Cascade Call related to the Program “National Center for Gene Therapy and Drugs based on RNA Technology (CN RNA & GENE THERAPY) – Spoke 6” CN00000041, CUP B83C22002860006;

Start date: 18/07/2024

End date: 19/11/2025

Total NRRP funding for the cascade call: € 390.000,00

Total NRRP funding for Unipr: € 390.000,00

The POP N ART project, led by the University of Parma, focuses on developing polyfunctional peptide nucleic acids (PNAs) for precision RNA targeting and modulation of interactions with proteins. The project aims to create modified PNAs with enhanced biological stability and sequence selectivity, capable of targeting and degrading specific RNAs. This initiative is part of the broader Spoke 6 RNA Drug Development program under the National Center for Gene Therapy and Drugs Based on RNA Technology. The project involves designing and synthesizing PNAs with various modifications, including chiral backbones and reactive groups, to improve RNA recognition and enable intracellular reactions. The ultimate goal is to provide advanced tools for RNA silencing and gene expression modulation, contributing to the development of new therapeutic approaches.

The project is structured into three work packages (WPs). WP1 focuses on the design and synthesis of modified PNAs with increased RNA recognition and environmental sustainability. WP2 aims to develop PNAs containing photoactivatable groups for intracellular reactions, enhancing RNA silencing effects. WP3 involves creating PNAs with functional groups for RNA degradation and studying their interactions with proteins. The project will leverage advanced molecular dynamics and high-performance computing to model these interactions and optimize PNA design. The outcomes will provide innovative knowledge in RNA-targeting and PNA-protein interactions, with potential applications in high-precision RNA targeting and gene therapy.

The University of Parma is involved in the following WP (work packege):

• WP1: Modified PNAs and their ‘green synthesis’
• WP2: PNA containing (photo)activatable groups
• WP3: PNAs containing functional groups to control RNA cleavage and protein interaction

• Department of Chemistry, Life Sciences and Environmental Sustainability

The POP N ART project expects to produce a series of advanced PNAs with improved RNA recognition and stability, capable of precise RNA targeting and degradation. These PNAs will be designed to discriminate target sequences down to a single nucleotide, enhancing their therapeutic potential. The project aims to demonstrate the effectiveness of these PNAs in gene expression modulation and RNA silencing, providing valuable tools for developing new RNA-based therapies. Additionally, the project will develop environmentally sustainable synthetic methodologies for PNA production, reducing the environmental impact of these processes.

Furthermore, the project aims to generate significant insights into PNA-protein interactions, which are crucial for understanding the broader biological implications of PNA-based therapies. By studying these interactions in detail, the project will identify potential off-target effects and optimize PNA design to minimize them. The successful development of these advanced PNAs and their validation in cellular models will pave the way for future clinical applications, contributing to the advancement of RNA therapeutics and personalized medicine. The project's findings will be disseminated through scientific publications and collaborations, enhancing the impact of this innovative research.

National Center for Gene Therapy and Drugs based on RNA Technology (rna-genetherapy.eu)